The Emergence of Virtual Tumor Boards in Neuro-Oncology: Opportunities and Challenges

Abstract

Background
Virtual tumor board (VTB) platforms are an important aspect of cancer management. They enable easier access to a multidisciplinary team of experts. To deliver high-quality cancer care, it is necessary to coordinate numerous therapies and providers, share technical knowledge, and maintain open lines of communication among all professionals involved. The VTB is an essential tool in the diagnosis and treatment of brain cancer. For patients with glioma and brain metastases, multidisciplinary tumor board guidelines should guide diagnosis and therapy throughout the course of the illness. VTBs are an emerging resource across various cancer care networks in the United States.
Methodology
We performed a systematic search of all VTBs incorporating a platform designed for this specific role. We reviewed the records of the Genomet VTB, the Medical University of South Carolina (MUSC) VTB, and Xcures VTB. Summary data examined included the year of launch, demographics, characteristics of cases, average response time, advantages, and how they handle protected health information.
Results
Overall, 30% of VTBs examined were launched in 2017. All had a Health Insurance Portability and Accountability Act-compliant online environment. On a review of Xcures records, the median age of the female patients was 57 years and the median age of the male patients was 55 years. The data showed that 44% (4.4 out of every 10 patients) with a confirmed treatment chose the VTB integrated option. Overall, 76% of patients in the Xcures registry had primary central nervous system tumors, with at least 556 patients in the tumor registry which included 46% glioblastoma cases (96% primary, 4% secondary). In the MUSC VTB project, 112 thoracic tumor cases and nine neuro-oncology cases were reviewed. The tumor board met weekly, and the average response time was within 24 hours of case review and presentation. The Genomet VTB de-identifies all patient information; this is a virtual platform primarily focused on neuro-oncology cases. Cases involved a median of five specialists most commonly neuro-oncologists, neurosurgeons, radiation oncologists, molecular pathologists, and neuroradiologists. The case review revealed an age range of six months to 84 years (mean age = 44.5 years), with 69.6% males and 30.4% females, 43.5% glioblastomas, 8.7% adenocarcinomas, and 8.7% infratentorial tumors. The average response time observed in all cases was ≤24 hours.
Conclusions
VTBs allow for quicker expert analysis of cases. This has resulted in an accelerated number of cases reviewed with a shortened communication time. More studies are needed to gain additional insights into user engagement metrics.

Full text

Review began 05/30/2022
Review ended 06/05/2022
Published 06/06/2022
© Copyright 2022
Ekhator et al. This is an open access article
distributed under the terms of the Creative
Commons Attribution License CC-BY 4.0.,
which permits unrestricted use, distribution,
and reproduction in any medium, provided
the original author and source are credited.
The Emergence of Virtual Tumor Boards in
Neuro-Oncology: Opportunities and Challenges
Chukwuyem Ekhator , Santosh Kesari , Ramya Tadipatri , Ekokobe Fonkem , Jai Grewal
1. Medicine, New York Institute of Technology, College of Osteopathic Medicine, Glen Cove, USA 2. Translational
Neurosciences, Pacific Neuroscience Institute, Santa Monica, USA 3. Neurology, Barrow Neurological Institute,
Phoenix, USA 4. Neuro-Oncology, Baylor Scott & White Medical Center - Temple, Phoenix, USA 5. Neuro-Oncology,
Mount Sinai South Nassau Hospital, Oceanside, USA
Corresponding author: Chukwuyem Ekhator, chukkiecmd@gmail.com
Abstract
Background
Virtual tumor board (VTB) platforms are an important aspect of cancer management. They enable easier
access to a multidisciplinary team of experts. To deliver high-quality cancer care, it is necessary to
coordinate numerous therapies and providers, share technical knowledge, and maintain open lines of
communication among all professionals involved. The VTB is an essential tool in the diagnosis and
treatment of brain cancer. For patients with glioma and brain metastases, multidisciplinary tumor board
guidelines should guide diagnosis and therapy throughout the course of the illness. VTBs are an emerging
resource across various cancer care networks in the United States.
Methodology
We performed a systematic search of all VTBs incorporating a platform designed for this specific role. We
reviewed the records of the Genomet VTB, the Medical University of South Carolina (MUSC) VTB, and Xcures
VTB. Summary data examined included the year of launch, demographics, characteristics of cases, average
response time, advantages, and how they handle protected health information.
Results
Overall, 30% of VTBs examined were launched in 2017. All had a Health Insurance Portability and
Accountability Act-compliant online environment. On a review of Xcures records, the median age of the
female patients was 57 years and the median age of the male patients was 55 years. The data showed that
44% (4.4 out of every 10 patients) with a confirmed treatment chose the VTB integrated option. Overall, 76%
of patients in the Xcures registry had primary central nervous system tumors, with at least 556 patients in
the tumor registry which included 46% glioblastoma cases (96% primary, 4% secondary). In the MUSC VTB
project, 112 thoracic tumor cases and nine neuro-oncology cases were reviewed. The tumor board met
weekly, and the average response time was within 24 hours of case review and presentation. The Genomet
VTB de-identifies all patient information; this is a virtual platform primarily focused on neuro-oncology
cases. Cases involved a median of five specialists most commonly neuro-oncologists, neurosurgeons,
radiation oncologists, molecular pathologists, and neuroradiologists. The case review revealed an age range
of six months to 84 years (mean age = 44.5 years), with 69.6% males and 30.4% females, 43.5%
glioblastomas, 8.7% adenocarcinomas, and 8.7% infratentorial tumors. The average response time observed
in all cases was ≤24 hours.
Conclusions
VTBs allow for quicker expert analysis of cases. This has resulted in an accelerated number of cases reviewed
with a shortened communication time. More studies are needed to gain additional insights into user
engagement metrics.
Categories: Neurology, Neurosurgery, Oncology
Keywords: glioblastoma, neurology, neuro-oncology, cns tumor, virtual tumor board
Introduction
Virtual tumor board (VTB) platforms are an important aspect of cancer management. They enable easier
access to a multidisciplinary team of experts. To deliver high-quality cancer care, it is necessary to
coordinate numerous therapies and providers, share technical knowledge, and maintain open lines of
communication among all professionals involved. The VTB is an essential tool in the diagnosis and
treatment of brain cancer. For patients with glioma and brain metastases, multidisciplinary tumor board
guidelines should guide diagnosis and therapy throughout the illness course. VTBs are an emerging resource
across various cancer care networks in the United States. Standard and effective healthcare delivery has
become more important as the number and complexity of cancer cases have grown exponentially over the
1 2 3 4 5
Open Access Original
Article DOI: 10.7759/cureus.25682
How to cite this article
Ekhator C, Kesari S, Tadipatri R, et al. (June 06, 2022) The Emergence of Virtual Tumor Boards in Neuro-Oncology: Opportunities and Challenges.
Cureus 14(6): e25682. DOI 10.7759/cureus.25682

last several decades [1]. VTBs provide a platform for experts from various fields to get together and discuss
how to best implement treatment protocols [2].
Coordinating numerous therapies and providers, sharing technical knowledge, and maintaining open lines
of communication among all professionals involved are crucial for high-quality cancer care [3,4]. According
to Gross’s definition of hospital tumor boards, which first appeared in 1987 [5], tumor boards are
multidisciplinary teams of doctors who meet regularly to review cancer cases in order to improve the care of
cancer patients in their community by exchanging information between participating physicians. The
number of tumor boards has expanded tremendously since then, notably in the past 10 years, as their
effectiveness in increasing diagnostic accuracy, adherence to clinical practice standards, and clinical
outcomes has been proven.
In addition, VTB consultations enhance cancer patients’ access to the most recent cancer management plans
and offer a tool for evaluating the quality of professional treatment provided by healthcare providers [6].
There is a wide range of professionals working together on a tumor board, ranging from thoracic surgeons to
medical oncologists, radiologists, pulmonologists, pathologists, and molecular scientists. Nuclear medicine,
nutrition, palliative and rehabilitation medicine, patient advocacy, research nursing, or other experts may be
included in the expanded board [7]. In academic institutions, students and postdoctoral fellows may also be
included [8].
The coronavirus disease 2019 (COVID-19) pandemic has changed the way patients are approached [9]. It is
becoming more challenging to obtain a comprehensive health consultation. Therefore, the adoption of
telemedicine such as VTBs may prevent any delay in the modification of care coordination in this moment of
crisis [10]. Additionally, the notion of virtualization is being included in the design of cancer treatment
because it may reduce geographic boundaries and simplify clinical communication and decision-making.
However, videoconferencing technology, aided by the COVID-19 pandemic, has permitted the formation of
VTBs in many cancer institutes and hospitals [11,12]. Meetings via the internet allow healthcare
practitioners to work together more efficiently by reducing the time spent on travel as well as other
associated costs [12,13].
A multidisciplinary team approach to diagnosis, therapy, and follow-up care in neuro-oncology is critical
due to the complexity of the disease. Oncological staging and treatment approaches are constantly evolving,
and a multidisciplinary meeting is becoming more important [14]. As a quality checkpoint, the primary goal
of these meetings is to guarantee that each case is thoroughly evaluated, regardless of whether it is
pretreatment, during treatment, or posttreatment. Treatment planning, clinical trial enrolment, care
coordination, management of treatment problems, evaluation of the disease response, recurrence
monitoring, and survivorship outcomes are all part of this process [15].
Pretreatment assessment [16], accurate staging [17,18], and timely treatment [19-21] may be improved by the
implementation of VTBs. Other factors may include disease-specific factors and overall survival [22-24];
however, there is some debate around this. Academic institutions are starting to analyze the quality metrics
of these VTBs in relation to guideline adherence and clinical outcomes as the use of these meetings has
become more common and this approach has become the standard of therapy [23].
VTBs have been implemented in various clinical settings for better evaluation of different cancers, including
those of the lungs [13], liver [25], breast [11], gastrointestinal tract [11], and head and neck [26], in the last
decades where the implementation of these board meetings resulted in enhanced referral coordination [27],
shorter diagnostic and treatment latencies [13,25,27], increased prevalence of board evaluations [25], and
decreased patient and clinician transport burden [25,27].
The VTB is an essential tool in the diagnosis and treatment of brain cancer. For patients with glioma and
brain metastases, multidisciplinary tumor board guidelines should guide diagnosis and therapy throughout
the illness course. For a tumor board in neuro-oncology, there seems to be a paucity of information in the
medical literature. This may be due in part to the specific training required for neuro-oncologists,
neuroradiologists, and pathologists in this discipline [28-30].
To better serve patients with cancer, VTBs have developed over the years into more collaborative structures
with teams that focus on rehabilitation, psychological well-being, and long-term care. Patients may also be
present at these sessions, and it is important to have their input at each stage of the therapy. In addition,
the members of the tumor boards share treatment choices and clinical responsibilities. Technology has made
it simpler for VTB members to collaborate through a secured interface precluding the need for a face-to-face
meeting [31]. The objective of this study is to provide a summary of a systematic review of VTBs and their
implementation in neuro-oncology.
This article was previously presented as a meeting abstract at the 2022 American Academy of Neurology
(AAN) Annual Scientific Meeting on April 5th, 2022.
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Materials And Methods
We performed a systematic search of all VTBs incorporating a platform designed for this specific role. We
reviewed the records of the Genomet VTB, the Medical University of South Carolina (MUSC) VTB, and Xcures
VTB. Summary data examined include the year of launch, demographics, characteristics of cases, average
response time, advantages, and how they handle protected health information.
Results
On a review of Xcures records, the median age of female patients was 57 years and the median age of male
patients was 55 years. The data showed that 44% (4.4 out of every 10 patients) with a confirmed treatment
chose the VTB integrated option. Overall, 76% of patients in the Xcures registry had primary central nervous
system (CNS) tumors. There were at least 556 patients in the tumor registry which included 46%
glioblastoma cases (96% primary; 4% secondary), 13% diffuse midline glioma with histone H3 lysine27-to-
methionine (H3K27M)-mutant cases, 5% diffuse intrinsic pontine glioma cases, 3% astrocytoma and diffuse
astrocytoma cases, 3% anaplastic astrocytoma cases, 3% glioma and diffuse glioma cases, 1% anaplastic
oligodendroglioma cases, and <1% gliosarcoma, oligodendroglioma, pilocytic astrocytoma, anaplastic
pleomorphic xantoastrocytoma, fibrillary astrocytoma, oligoastocytoma, and pleomorphic
xanthoastrocytoma cases. Tumor locations were distributed as 33% frontal, 19% parietal, 26% temporal, 4%
occipital and 3% multifocal, 3% temporoparietal, 3% frontotemporal and thalamus, 2% frontoparietal, 1%
parietal occipital, bifrontal, and corpus callosum, and <2% others.
In the MUSC VTB project, 112 thoracic tumor cases and nine neuro-oncology cases were reviewed. The
tumor board met weekly, and the average response time was within 24 hours of case review and
presentation. Patient information was uploaded through a secured patient portal access. Patient
demographics were not recorded.
The Genomet VTB de-identifies all patient information; this is a virtual platform primarily focused on
neuro-oncology cases. Cases involved a median of five specialists most commonly neuro-oncologists,
neurosurgeons, radiation oncologists, molecular pathologists, and neuroradiologists. Participants had an
average of ≥257 cases reviewed. Case review revealed an age range from six months to 84 years (mean age =
44.5 years), with 69.6% males and 30.4% females, 43.5% glioblastoma cases, 8.7% adenocarcinoma cases,
8.7% infratentorial tumor cases, and <5% each of pineoblastoma, melanoma, hemangioblastoma, and
pilocytic astrocytoma cases. The average response time observed in all cases was ≤24 hours (Table 1).
Virtual
tumor
board
Xcures and cancer commons Genomet
Medical
University of
South Carolina
Year of
launch 2019 2017 2011
Approximate
number of
cases
≥556 257
112 thoracic and 9
neuro-oncology
cases
Summary
The median age of female patients was 57 years
and of male patients was 55 years. Overall,
2.44% of patients preferred the virtual tumor
board integrated treatment option
Each case reviewed involved a median of five
specialists most commonly neuro-oncologists,
neurosurgeons, radiation oncologists, molecular
pathologists, and neuroradiologists
Provides specialty
consultation
remotely for
patients with brain
tumors
Protected
health
information
handling
method
Health Insurance Portability and Accountability Act-compliant online environment
Advantages
Reduced tumor board preparation time by more than 90%. Patients receive the benefit of multispecialty consultation.
Integrated case-by-case expert analysis and shortened communication and response time. Improved productivity with data
and documentation
TABLE 1: Summary of virtual tumor board characteristics.
Discussion
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The use of tumor boards, as the benchmark in cancer care choice, has been extensively adopted. As handling
cancer takes a lot of time and effort, and the prevalence of cancer is on the rise, this has put a lot of pressure
on cancer treatment facilities, which are already stretched thin. As tumor care becomes more personalized,
the formation of specialist tumor boards, such as neuro-oncological tumor boards, looks to be a worthy
endeavor [32,33].
In neuro-oncology, VTBs have demonstrated advantages in both treatment and clinical outcomes. Other
advantages include the opportunity for physicians to receive ongoing education and training, as well as the
opportunity for them to reflect on their treatment strategies on a continuous basis. In addition, these VTBs
have the potential to involve patients in clinical trials [29,30,34].
In this study including three VTBs, we found variability in the boards with respect to data regarding the
demographics, characteristics of cases, average response time, and the way they handled protected
information. Complex diagnostic information and treatment choices need technologies that assist organized
codification, visualization, and interpretation of clinical data. Consequently, several academic fields,
including psychology, improvement science, and organizational science, are producing more research on
how to enhance tumor boards’ implementation. Even in more complicated instances, the advantages of
VTBs become evident, leading to adjustments in treatment strategies and better results. Smart systems that
can properly integrate, analyze, and comprehend clinical data are becoming more important as the amount
and complexity of available data keep growing [35].
Henderson et al. [36] reported a case of a five-year-old boy with a history of vomiting for two months which
was followed by headaches that worsened over time. There were no neurological deficits on examination,
but the magnetic resonance imaging (MRI) showed a cystic lesion with obstructive hydrocephalus. Subject to
the location of the tumor and associated obstructive hydrocephalus, the attending surgeon desired input
from the tumor board. Even though the condition of hydrocephalus did not require assistance, the treatment
approach (ventriculoperitoneal shunting versus endoscopic third ventriculostomy), the timing of treatment
in anticipation of possible craniotomy, and the approach adopted in the event of surgical treatment all had
risk and benefit considerations. With the help of a VTB (Genomet, New York), the de-identified case profile
was developed online and communicated with a voluntary network of neurosurgeons located in the United
States through an online email connection. Within 12 hours, three surgeons replied with clinical feedback
on the case. In accordance with their suggestions, the patient underwent an endoscopic third
ventriculostomy and was released home the next day without experiencing any headaches. After a few
months, the patient intended to return for tumor excision. The study presents some cases from a neuro-
oncological viewpoint where the implementation of VTBs was mandatory to personalize treatment by
involving experts from different fields in the VTB.
Case studies discussed in VTBs
Case 1
A six-month-old, full-term male presented with three weeks of abnormal eye movements and one day of left
periorbital swelling and clear ocular discharge. An examination demonstrated left cranial nerve (CN) III and
VI palsies and left lateral eyelid swelling and ptosis. Imaging revealed a diffusion-restricted suprasellar mass
without metastatic disease. A biopsy was undertaken (resection was deemed high risk) and demonstrated a
CNS embryonal tumor (WHO grade 4) with somatic mutations in retinoblastoma 1 (RB1) and mutY DNA
glycosylase (MUTYH). Methylation analysis identified the tumor as a pineoblastoma group A/PB-RB1
subgroup (even though the tumor was not located in the pineal gland) (Figure 1). Initial treatment consisted
of (1) one cycle per HEADSTART IV (cisplatin, cyclophosphamide, etoposide, IV methotrexate, and
vincristine): complicated by bronchospasm (secondary to etoposide), pericardial effusion leading to
tamponade physiology (led to heart failure and pulseless electrical activity (PEA) cardiac arrest requiring
venoarterial extracorporeal membrane oxygenation (VA-ECMO)); imaging demonstrated a slight decrease in
tumor size. (2) One cycle per ACNS0334 A (cisplatin, 50% dose-reduced cyclophamide, etoposide, and
vincristine): complicated by thrombotic microangiopathy (secondary to cisplatin) leading to renal
insufficiency, hypertensive urgency, severe hemolytic anemia and thrombocytopenia, and pulmonary edema
requiring bilevel positive airway pressure (BiPAP); imaging demonstrated a near-complete tumor response.
(3) Nine cycles of metronomic therapy (PO cyclophosphamide, etoposide, and temozolomide alternating
with PO celecoxib and isotretinoin; q4 week IT topotecan).
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FIGURE 1: (A) Brain MRI at diagnosis showing a suprasellar mass (red
arrow). (B) Best response to first-line therapy: brain MRI (red arrow)
showing suprasellar mass regression. (C) First recurrence brain MRI
(red arrow). (D) First recurrence spine MRI (red arrow). (E) Best
response to second-line therapy: brain MRI. (F) Second recurrence
spine MRI. (I) H&E stain showing WHO grade 4 CNS embryonal tumor.
(J) IHC showing strong synaptophysin expression. (K) H&E showing
scattered rosettes.
MRI: magnetic resonance imaging; H&E: hematoxylin and eosin; WHO: World Health Organization; CNS: central
nervous system; IHC: immunohistochem ical
The first recurrence was observed after nine cycles (six months) of metronomic therapy, with imaging
demonstrating local and distant recurrence. Salvage treatment was initiated with carboplatin, etoposide, and
ifosfamide and was complicated by seizures (likely secondary to the metastatic tumor but potentially
triggered by ifosfamide neurotoxicity); hence, ifosfamide was replaced with cyclophosphamide for the
following two cycles. Imaging after cycle two demonstrated a near-complete tumor response. Even though
the plan was to collect autologous stem cells, cells could not be mobilized. The second recurrence was
observed after three cycles of salvage therapy, with imaging again demonstrating new diffuse
leptomeningeal disease. Palliative treatment with PO etoposide was initiated and then transitioned to
gefitinib.
Several complications were associated with the case and the resection was deemed to be high risk because of
complications. Second, the adverse outcome of treatments necessitated input from different experts,
including neuro-oncologists, neurosurgeons, radiation oncologists, molecular pathologists, and
neuroradiologists.
Case 2
There was another case of an 18-year-old male who developed progressive back pain and paraesthesia
starting in April 2017. As this worsened, he underwent imaging in October 2017 and was found to have a
thoracic spinal mass. At the time, he was ambulatory with mild foot weakness only. He underwent a surgical
resection on October 5, 2017, and was diagnosed with a WHO grade 1 ganglioglioma. He subsequently
developed syringomyelia, lost leg strength and his ability to walk, and developed bowel and bladder
incontinence. He then underwent a second surgical operation on June 11, 2018. The diagnosis was updated
to a high-grade WHO grade 4 glioma with the presence of the H3K27M point mutation. The neuronal
elements previously described were no longer evident. He underwent radiation to the thoracic spine tumor
from July 2, 2018, to August 5, 2018, receiving 1.8 Gy in 28 fractions. A molecular profile was ordered from
the second surgical specimen.
He received one cycle of the combination of temozolomide and CCNU as initial therapy in August 2018. The
molecular report became available on September 30, 2019. Due to the presence of fibroblast growth factor
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receptor 1 (FGFR1) and neurofibromatosis type 1 (NF1) mutations, temozolomide + CCNU was discontinued
(without evidence of progression) and sorafenib monotherapy was initiated at 400 mg PO twice daily. The
patient experienced clinical and radiographic benefits for approximately six months. After this time (March
11, 2019), there appeared to be imaging progression, and FOLFIRI (5-fluorouracil, irinotecan, folate) was
added to sorafenib. He took FOLFIRI + sorafenib from July 10, 2019, to September 1, 2019. He presented for
treatment recommendations in the setting of his molecular findings. He did not wish to consider surgical
options. Neurologically, he had no leg strength (0/5) and impaired bowel and bladder function but
progressively improved and was fully able to use his arms to transfer and perform self-catheterization. The
patient underwent his first surgery of spinal cord tumor resection with extensive instrumentation in
Norway. The patient was neurologically stable immediately postoperatively but later developed
syringomyelia. The patient then underwent re-resection due to tumor progression. Pathological diagnosis
was updated to high-grade glioma, H3K27M. Subsequently, radiation therapy was initiated with an external
beam and was limited to the cervical and thoracic spine, with 50.4 Gy in 28 fractions, which resulted in
stable disease followed by progression. After that, systemic therapy was started with temozolomide 200
mg/m2 for five days + CCNU 110 mg/m2 for one day, which led to stable disease, followed by a second
systemic therapy course with sorafenib 400 mg BID, chosen due to the presence of FGFR1 and NF1
mutations, which resulted in partial response followed by progression. A third systemic therapy was started
with sorafenib 400 mg BID + FOLFIRI, which resulted in stable disease followed by progression. The patient
was resistant to topoisomerase inhibitors, sorafenib, and FOLFIRI, and he was not a candidate for surgical
options. The patient’s tumor mutational burden score indicated eight mutations, and his Karnofsky
Performance Status (KPS) score was 40. Molecular findings are summarized in Table 2.
Molecular
finding Variant interpretation Tissue
tested
H3K27M
mutation
Mutations in H3F3A, which encodes histone H3.3, commonly occur in pediatric glioblastoma. Additionally, H3F3A
K27M substitutions occur in gliomas that arise at midline locations (e.g., pons, thalamus, spine); moreover, this
substitution occurs mainly in tumors among children and adolescents
Spinal
cord
NF1
deletion
Neurofibromin, the protein product of NF1, regulates the inactivation of the Ras pathway and acts as a tumor
suppressor. Recent studies have identified somatic alterations in the gene encoding for neurofibromin (NF1 ) in a
subset of glioblastoma (GBM), usually associated with the mesenchymal molecular subtype. NF1 loss was
associated with worse overall and disease-specific survival in the lower-grade glioma, but not the GBM group in the
Cancer Genome Atlas cohort. IDH1 or 2 mutations co-existed in lower-grade gliomas with NF1 loss (36%) but not in
GBM
Spinal
cord
MS1-H
No identifiable defects of mismatch repair. Microsatellite instability (MSI) is a pattern of hypermutation that occurs at
genomic microsatellites and is caused by defects in the mismatch repair system. Mismatch repair deficiency that
leads to MSI has been well described in several types of human cancer, most frequently in colorectal, endometrial,
and gastric adenocarcinomas
Un-
methylated
MGMT
MGMT (0-6 methylguanine DNA methyltransferase) is a DNA-repair enzyme which repairs the naturally occurring
or therapeutically induced mutagenic DNA lesion 06-methylguanine back to guanine and prevents mismatch and
errors during DNA replication and transcription. Tumor MGMT methylation is predictive of increased benefit from
DNA damaging therapies, such as radiation therapy and temozolomide, as well as generally prognostic for survival.
In large, randomized trials, GBM patients with MGMT-methylated tumors had improved prognosis (longer survival)
than patients who are unmethylated
Spinal
cord
IDH
wildtype
IDH1 R132H point mutations are generally associated with secondary GBM and more indolent tumor behavior than
tumors that are IDH1 wildtype. IDH1 status is a component of the WHO 2016 criteria for certain astrocytomas
including GBM. IDH is an enzyme that normally converts isocitrate to alpha-ketoglutarate as part of the TCA cycle
TABLE 2: Summary of molecular findings identified in virtual tumor board cases.
IDH: isocitrate dehydrogenase; MGMT: methylguanine-DNA methyltransferase; MSI-H: microsatellite instability-high; NF-1: neurofibromin-1
The repetitive progression of the disease after every treatment approach and the resistance to drugs required
input from several experts on a VTB platform to personalize treatment according to the molecular findings.
Case 3
Another case discussed by the online VTB Genomet was the case of a 56-year-old male with progressive,
octreotide-positive meningioma who presented for medical salvage treatment options. He underwent two
resections, intensity-modulated radiation therapy (IMRT), and two courses of stereotactic surgery (SRS).
Chemotherapy with sunitinib was switched to bevacizumab due to intractable hand and foot syndrome. He
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had mild right leg weakness with a KPS score of 70. The patient underwent craniotomy and resection of left
interhemispheric meningioma with no postoperative complications, followed by another surgery after four
years for seizure and intractable cerebral edema and right leg weakness. Small wound dehiscence resolved
by four weeks postoperatively. Pathology showed WHO grade 1 with low mitotic activity (<10%) (Figure 2).
He was started on radiation therapy after three months with IMRT 5,600 cGy in 28 fractions, which was
tolerated well and showed a partial response followed by progression. A second radiation therapy course was
started with GammaKnife SRS receiving 16 Gy single fraction, which also resulted in partial response
followed by progression. A third radiation therapy course was started with Novalis TX SRS receiving 22.5 Gy
in five fractions, which resulted in stable disease followed by progression. He developed grade 4 hand and
foot syndrome requiring discontinuation after treatment break, dose reduction, and unsuccessful re-
challenge. There was a partial response followed by progression. A second systemic therapy course was
started with bevacizumab 10 mg/kg every two weeks; eight cycles (14 days) were completed. He had stable
disease after four cycles, but progression was observed. PEGylated interferon-alpha was not administered
due to toxicity/adverse events and risk of injury.
FIGURE 2: H&E stain showing WHO grade 1 meningothelial
meningioma.
H&E: hematoxylin and eosin; WHO: World Health Organization
Case 4
Another case presented was of a 28-year-old female who presented with headaches, dizziness, and visual
impairment, followed by gait ataxia. MRI revealed an oval expansive formation in the brainstem, a
hypointense signal in T1, isointense on fluid-attenuated inversion recovery (FLAIR), and hyperintense on
other sequences with a nodular focus of contrast enhancement measuring 3.2 × 2.3 × 2.3 cm located in the
brainstem at the level of the bulb medullary transition, compressing the cerebrospinal column at the level of
the foramen magnum (Figure 3). There was no evidence of hyperperfusion. Biopsy showed pilocytic
astrocytoma, WHO grade I, glial fibrillary acidic protein (GFAP)-positive; inconclusive synaptophysin;
negative for neurofilament, isocitrate dehydrogenase (IDH1), and p53 mutation. Ki67 was 5%.
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FIGURE 3: (A) Sagittal T1: hypointense cystic brain stem mass (red
arrow). (B) Axial T1+C: nodular enhancement (red arrow). (C) Axial T2
FLAIR: iso/hyperintense (red arrow). (D) Axial T2: hyperintense (red
arrow).
FLAIR: fluid-attenuated inversion recovery
Subject to the findings and examination, only a biopsy was possible in this case and radiotherapy was
contraindicated due to risk. Guidance from tumor board experts was needed with respect to the systemic
therapy in this case.
Case 5
Another case was of an 84-year-old female who presented with subacute hearing loss, confirmed on
audiometry. Brain imaging revealed a right cerebellopontine angle (CPA)-enhancing mass. The diagnosis
was of an acoustic schwannoma of the brain, infratentorial, WHO grade 1. The patient underwent surgical
resection of the right CPA mass, presumably acoustic schwannoma. Other therapies were rejected due to the
risk of toxicity/adverse events and risk of injury. Comorbidities included kidney disease, hypertension, and
diabetes, and the patient’s Eastern Cooperative Oncology Group (ECOG) Performance Score was 1. The
patient’s axial and coronal scans are shown in Figure 4.
FIGURE 4: Axial radiological scan (A) (acoustic schwannoma at the
cerebellopontine angle) and coronal radiological scan (B) (acoustic
schwannoma at the cerebellopontine angle).
Case 6
Another case discussed was that of a 73-year-old female as a newly diagnosed patient with subtotal resected
left occipital glioblastoma who presented for additional treatment recommendations. She was diagnosed
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with glioblastoma, IDH-wildtype, WHO grade 4, in the brain. She underwent subtotal resection of a left
occipital glioblastoma, and there were no other complications. Comorbidities included kidney disease and a
history of a liver transplant. The patient was resistant to alkylating agents and had a KPS score of 50. Her
molecular findings are shown in Figure 5.
FIGURE 5: Radiological image showing a left occipital well-
circumscribed mass (red arrow) in different sections outlined in A, B,
and C (glioblastoma and IDH-wildtype).
IDH: isocitrate dehydrogenase
Opportunities and challenges in the implementation of VTBs
Implementation of VTBs in neuro-oncology has demonstrated effectiveness in unraveling certain treatment
crossroads. All the cases presented above required input and consultation with a multidisciplinary tumor
board. The complexities in the cases necessitated guidance with respect to each approach to be adopted,
including surgery, radiation therapy, and systemic therapy. VTBs have been utilized effectively in various
countries and specialties, including gynecologic oncology, since at least 2004, despite being novel in the
context of neuro-oncology [37]. A study on the automation of VTBs reported a twofold increase in the
number of cases evaluated each month. In addition, VTBs provided more possibilities than a lab report
alone. In 503 of the 642 patients, VTBs allowed for genomic-based treatment choices to be made available to
78.6% of patients. In total, 229 and 80 patients received on-label and off-label therapy recommendations,
respectively, based on proteomic data. Importantly, VTBs skipped therapy alternatives in 64% of individuals
who had established resistance to earlier treatments.
Implementing a VTB program has been fraught with difficulties, including credible technical setup [13,27],
expanded duration of virtual case presentations [1], scarcity of community-based caseloads [11], delays in
obtaining supportive evidence [11], and the high cost of virtual information technology facilities [11,38].
Despite these obstacles, it seems that VTB participants in general either support it or find it equivalent to
regular in-person meetings concerning effectiveness and efficiency [1,11,26]. The degree to which VTBs
influence guideline compliance and clinical outcomes in contrast to a standard tumor board is yet to be
determined by researchers. It will be possible to discern these links when more data on the development of
VTB quality become available [12].
One downside of using a VTB is the absence of physical connection while discussing patient care issues with
other members of the VTB. There is a consequent decline in the sense of brotherhood among physicians
across specializations. Additionally, while utilizing videoconferencing software, it might be difficult to have
engaged discussions with numerous speakers at once. Software issues, such as screen sharing and audio
problems, were the most challenging to overcome, particularly during the initial VTB sessions held online.
However, in future sessions, this was made more acceptable. Finally, some participants reported that it was
more difficult to keep track of the list of patients mentioned during the VTB session than others [12].
The fundamental drawback of this study, which is also true of all surveys, is the inability to generalize the
findings based on the sample of VTBs enrolled in the study. Another limitation of VTBs is obtaining metrics
from individual VTBs as most of their metrics are unpublished. For a VTB to be successful and sustainable, it
must go through a process in which various parts of the application are regularly examined, allowing for
improvements before it can be widely used. Additional considerations for adoption include privileging,
credentialing, and financial considerations, among other things.
Conclusions
VTBs have allowed for quicker expert analysis of cases. This has resulted in an accelerated number of cases
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reviewed with a shortened communication time. Its implementation in neuro-oncology and other
specialized fields will result in personalized healthcare provision in collaboration with experts from different
disciplines. More studies are needed to obtain additional insights into user engagement metrics.
Additional Information
Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All
authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In
compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services
info: All authors have declared that no financial support was received from any organization for the
submitted work. Financial relationships: Santosh Kesari declare(s) personal fees and stock/stock options
from Xcures. Santosh Kesari is a consultant to Xcures, receives consulting fees, and has equity. Other
relationships: All authors have declared that there are no other relationships or activities that could appear
to have influenced the submitted work.
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